真鲷视网膜结构及其视觉特性研究：Ⅱ视网膜光感受细胞超微结构研究

对真鲷光感受细胞的超微结构进行观察,结果表明：视杆外段膜盘为游离膜盘,视锥外段膜盘则为连续的膜结构,视锥和视杆均含有连接纤毛和辅助外段。花萼状突起起源于内段。椭体内充满线粒体,无球状小体。双锥椭圆体并生膜为六层,视锥内段无鳍状突起,视锥突触带,在明适应视网膜中数量增多,在暗适应视网中数量减少,视杆突触带在这两种适应网膜中数量不变,每一杆小球只有一个突触带,而锥小足有４－６个突触带。     

Actin-dependent myoid elongation in teleost rod inner/outer segments occurs in the absence of net actin polymerization.

In the retinas of teleost fish, rod photoreceptors elongate in response to light. Light-activated elongation is mediated by the myoid of the rod inner segment and is actin-dependent. Inner segment F-actin filaments form bundles running parallel to the cell's long axis. We examined the mechanism of rod elongation using mechanically-detached rod fragments, consisting of the motile inner segment and sensory outer segment (RIS-ROS). When RIS-ROS are isolated from dark-adapted green sunfish and cultured in the light, they elongate 15 microns at 0.3-0.6 microns/min. Elongation was inhibited 65% by 0.1 microM Cytochalasin D, suggesting a requirement for actin assembly. To determine the extent of assembly during elongation, we used three approaches to measure the F-actin content in RIS-ROS: detection of pelletable actin by SDS-PAGE after detergent-extraction of RIS-ROS; quantification of fluorescein-phalloidin binding by fluorimetry, fluorescence-activated cell sorting and image analysis; estimation of total F-actin filament length by electron microscopy. All three assays indicated that no net assembly of RIS-ROS F-actin accompanied myoid elongation. An increase in F-actin content within the elongated myoid was counterbalanced by a decrease in F-actin content within the 13 microvillus-like calycal processes located at the end of the inner segment opposite to the growing myoid. O'Connor and Burnside (Journal of Cell Biology 89:517-524, 1981) showed that minus-ends of rod F-actin filaments are oriented towards the elongating myoid while plus-ends are oriented towards the shortening calycal processes. Our observations suggest that RIS-ROS elongation entails actin polymerization at the minus-ends of filaments coupled with depolymerization at the filament plus-ends.     

中国大鲵视网膜的光镜和扫描电镜研究

用光镜和扫描电镜观察了大鲵视网膜各类细胞的形态及分布, 对视细胞和节细胞进行计数。视网腊中三个核层及两个网状层分布均匀,无中央凹。每张视网膜的视细胞总数约130000,节细胞约8000,视杆与视锥之比为8.5：1。扫描电镜下,视杆外节表面的小叶间沟清晰;视杆视锥外节均有从内节伸出的20-30条萼状突起;核周体表面亦有20-30条细胞质突起。文中还报道了幼体视细胞的形态及密度。讨论了上述结构的机能。     

Ultrastructure of the distal retina of the adult zebrafish, Danio rerio

The organization, morphological characteristics, and synaptic structure of photoreceptors in the adult zebrafish retina were studied using light and electron microscopy. Adult photoreceptors show a typical ordered tier arrangement with rods easily distinguished from cones based on outer segment (OS) morphology. Both rods and cones contain mitochondria within the inner segments (IS), including the large, electron-dense megamitochondria previously described (Kim et al.) Four major ultrastructural differences were observed between zebrafish rods and cones: (1) the membranes of cone lamellar disks showed a wider variety of relationships to the plasma membrane than those of rods, (2) cone pedicles typically had multiple synaptic ribbons, while rod spherules had 1-2 ribbons, (3) synaptic ribbons in rod spherules were ∼2 times longer than ribbons in cone pedicles, and (4) rod spherules had a more electron-dense cytoplasm than cone pedicles. Examination of photoreceptor terminals identified four synaptic relationships at cone pedicles: (1) invaginating contacts postsynaptic to cone ribbons forming dyad, triad, and quadrad synapses, (2) presumed gap junctions connecting adjacent postsynaptic processes invaginating into cone terminals, (3) basal junctions away from synaptic ribbons, and (4) gap junctions between adjacent photoreceptor terminals. More vitread and slightly farther removed from photoreceptor terminals, extracellular microtubule-like structures were identified in association with presumed horizontal cell processes in the OPL. These findings, the first to document the ultrastructure of the distal retina in adult zebrafish, indicate that zebrafish photoreceptors have many characteristics similar to other species, further supporting the use of zebrafish as a model for the vertebrate visual system.     

p53 Selectively Regulates Developmental Apoptosis of Rod Photoreceptors

Retinal cells become post-mitotic early during post-natal development. It is likely that p53, a well-known cell cycle regulator, is involved in regulating the genesis, differentiation and death of retinal cells. Furthermore, retinal cells are under constant oxidative stress that can result in DNA damage, due to the extremely high level of metabolic activity associated with phototransduction. If not repaired, this damage may result in p53-dependent cell death and ensuing vision loss. In this study, the role of p53 during retinal development and in the post-mitotic retina is investigated. A previously described super p53 transgenic mouse that expresses an extra copy of the mouse p53 gene driven by its endogenous promoter is utilized. Another transgenic mouse (HIP) that expresses the p53 gene in rod and cone photoreceptors driven by the human interphotoreceptor retinoid binding protein promoter was generated. The electroretinogram (ERG) of the super p53 mouse exhibited reduced rod-driven scotopic a and b wave and cone-driven photopic b wave responses. This deficit resulted from a reduced number of rod photoreceptors and inner nuclear layer cells. However, the reduced photopic signal arose only from lost inner retinal neurons, as cone numbers did not change. Furthermore, cell loss was non-progressive and resulted from increased apoptosis during retinal developmental as determined by TUNEL staining. In contrast, the continuous and specific expression of p53 in rod and cone photoreceptors in the mature retinas of HIP mice led to the selective loss of both rods and cones. These findings strongly support a role for p53 in regulating developmental apoptosis in the retina and suggest a potential role, either direct or indirect, for p53 in the degenerative photoreceptor loss associated with human blinding disorders.     

Scanning electron microscopy of photoreceptor cells in the light- and dark-adapted retina of Haplochromis burtoni (Cichlidae,Teleostei)

Summary The photoreceptor layer in the retina of Haplochromis burtoni (Cichlidae, Teleostei) was studied by scanning electron microscopy. Three types of receptors were identified: rods, single-cones and double-cones. The three-dimensional arrangement of these photoreceptors is described in the light- and dark-adapted retina. The surface of the inner segment of the photoreceptor cells displays fine vertical fissures which give rise to slender processes. These so called calycal processes which are of different lengths in rods and cones, surround the beginning of the smooth-surfaced outer segment. The myoid, the contractile part of the receptor, which is located beneath the ellipsoid, was examined in the single-cones of the dark-adapted retina. It is a slender structure with surface infoldings. The myoid, studied by transmission electron microscopy, contains bundles of parallel myofilaments, which are thought to be contractile.This investigation was supported by grants of the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 51-E/10)     

Embryonic fissure and photoreceptor differentiation in the eye of adult Garra rufa Heckel 1843 (Cyprinidae, Teleostei)

The retina of the adult teleost Garra rufa retains a curved, open embryonic fissure indicating an asymmetrical postembryonic retinal growth. Undifferentiated, oval photoreceptors are observed on both sides of the middle of the fissure with their larger diameter running parallel to the fissure to which they may attach by desmosomes. They detach from the fissure, rotate to become perpendicular to it and begin an active process of differentiation as they slide along the temporal side of the outer half of the fissure. This process is divided into stages for simplicity. The photoreceptors develop stumpy inner segments extending into a ventricular space that appears between the retinal pigment epithelium and the photoreceptors. Calycal processes arise from the inner segments and the distal centriole of each photoreceptor forms a connecting cilium. The proximal centriole is retained for some time after the outer segment develops. The formation of rod spherules and cone pedicles takes place almost concomitantly with the outer segments. Double cones appear first as single cones before pairing. One or more of the principal cone mitochondria accumulate electron-dense material and merge to form the ellipsosome. The retinal pigment epithelium undergoes a parallel differentiation. The developmental events described in the present work conform those recorded in embryonic teleostean retinas.     

Myo3A,one of two class III myosin genes expressed in vertebrate retina,is localized to the calycal processes of rod and cone photoreceptors and is expressed in the sacculus

The striped bass has two retina-expressed class III myosin genes, each composed of a kinase, motor, and tail domain. We report the cloning, sequence analysis, and expression patterns of the long (Myo3A) and short (Myo3B) class III myosins, as well as cellular localization and biochemical characterization of the long isoform, Myo3A. Myo3A (209 kDa) is expressed in the retina, brain, testis, and sacculus, and Myo3B (155 kDa) is expressed in the retina, intestine, and testis. The tails of these two isoforms contain two highly conserved domains, 3THDI and 3THDII. Whereas Myo3B has three IQ motifs, Myo3A has nine IQ motifs, four in its neck and five in its tail domain. Myo3A localizes to actin filament bundles of photoreceptors and is concentrated in the calycal processes. An anti-Myo3A antibody decorates the actin cytoskeleton of rod inner/outer segments, and this labeling is reduced by the presence of ATP. The ATP-sensitive actin association is a feature characteristic of myosin motors. The numerous IQ motifs may play a structural or signaling role in the Myo3A, and its localization to calycal processes indicates that this myosin mediates a local function at this site in vertebrate photoreceptors.     

SPACRCAN, a novel human interphotoreceptor matrix hyaluronan-binding proteoglycan synthesized by photoreceptors and pinealocytes

The interphotoreceptor matrix is a unique extracellular complex occupying the interface between photoreceptors and the retinal pigment epithelium in the fundus of the eye. Because of the putative supportive role in photoreceptor maintenance, it is likely that constituent molecules play key roles in photoreceptor function and may be targets for inherited retinal disease. In this study we identify and characterize SPACRCAN, a novel chondroitin proteoglycan in this matrix. SPACRCAN was cloned from a human retinal cDNA library and the gene localized to chromosome 3q11.2. Analysis of SPACRCAN mRNA and protein revealed that SPACRCAN is expressed exclusively by photoreceptors and pinealocytes. SPACRCAN synthesized by photoreceptors is localized to the interphotoreceptor matrix where it surrounds both rods and cones. The functional protein contains 1160 amino acids with a large central mucin domain, three consensus sites for glycosaminoglycan attachment, two epidermal growth factor-like repeats, a putative hyaluronan-binding motif, and a potential transmembrane domain near the C-terminal. Lectin and Western blotting indicate an M(r) around 400,000 before and 230,000 after chondroitinase ABC digestion. Removal of N- and O-linked oligosaccharides reduces the M(r) to approximately 160,000, suggesting that approximately 60% of the mass of SPACRCAN is carbohydrate. Finally, we demonstrate that SPACRCAN binds hyaluronan and propose that associations between SPACRCAN and hyaluronan may be involved in organization of the insoluble interphotoreceptor matrix, particularly as SPACRCAN is the major proteoglycan present in this matrix.     

Fine structure of the retina of black bass, Micropterus salmoides (Centrarchidae, Teleostei).

The structure of light- and dark-adapted retina of the black bass, Micropterus salmoides has been studied by light and electron microscopy. This retina lacks blood vessels at all levels. The optic fiber layer is divided into fascicles by the processes of Müller cells and the ganglion cell layer is represented by a single row of voluminous cells. The inner nuclear layer consists of two layers of horizontal cells and bipolar, amacrine and interplexiform cells. In the outer plexiform layer we observed the synaptic terminals of photoreceptor cells, rod spherules and cone pedicles and terminal processes of bipolar and horizontal cells. The spherules have a single synaptic ribbon and the pedicles possess multiple synaptic ribbons. Morphologically, we have identified three types of photoreceptors: rods, single cones and equal double cones which undergo retinomotor movements in response to changes in light conditions. The cones are arranged in a square mosaic whereas the rods are dispersed between the cones.     

The fine structure of the parietal retinas of Anolis carolinensis and Iguana iguana

An electron microscopic examination of the parietal retinas of Anolis carolinensis and Iguana iguana demonstrated within each retina (1) two distinct populations of neurons, (2) two populations of glia, and (3) a population of photoreceptors which could not be subdivided. A small population of very electron-dense cells, in many respects similar to photoreceptors, was also found in the iguana. Correspondingly dark processes were found in the plexiform layer of each retina. Parietal photoreceptors generally resemble cones of the lateral eye. Glial cells were sub-classified on the basis of the location of their somata and the disposition of their processes. Neurons were identified by virtue of their cytology and their reception of axosomatic ribbon synapses from unidentified plexiform layer processes. Neuronal subtypes were located on opposite sides of the plexiform layer. Neurons distal to that layer were found to project the initial segments of their processes into the plexiform layer parallel to its long axis, while neurons central to the plexiform layer projected axons centrally and dendrites radially into the plexiform layer. The existence of at least two neuronal populations and of interphotoreceptor synapses suggests that photosensory processing within the parietal retina may be more complex than previously assumed.     

Posttranslational modifications of tubulin in teleost photoreceptor cytoskeletons

1. Posttranslational modifications of tubulin by acetylation and detyrosination have been correlated previously with microtubule stability in numerous cell types. 2. In this study, posttranslational modifications of tubulin and their regional distribution within teleost photoreceptor cones and rods are demonstrated immunohistochemically using antibodies specific for acetylated, detyrosinated, or tyrosinated tubulin. 3. Immunolocalization was carried out on isolated whole cones and mechanically detached rod and cone inner/outer segments. 4. Acetylated tubulin within rods and cones is found only in microtubules of the ciliary axoneme of the outer segment. Detyrosinated tubulin is also enriched in axonemes of both rod and cone outer segments. 5. Distributions of tyrosinated and detyrosinated cytoplasmic microtubules differ within cones and rods. In cones, detyrosinated and tyrosinated tubulins are both abundant throughout the cell body. In rods, the ellipsoid and myoid contain much more tyrosinated tubulin than detyrosinated tubulin. Comparisons between whole cones and cone fragments suggest that detyrosinated microtubules are more stable than tyrosinated microtubules in teleost photoreceptors. 6. Our findings provide further evidence that microtubules of teleost cones differ from rod microtubules in their stabilities and rapidity of turnover within the photoreceptor inner segment.     

Rhodopsin, 11-cis vitamin A, and interstitial retinol-binding protein (IRBP) during retinal development in normal and rd mutant mice

Biochemical and immunological techniques were used to determine the emergence of interstitial retinol binding protein (IRBP), rhodopsin, and stored retinyl esters (all-trans and 11-cis) during retinal development in normal and rd mice. IRBP could be demonstrated at embryonic Day 17 (E17), corresponding to an early stage of inner segment development. Although all-trans retinyl esters were present earlier, 11-cis retinyl esters did not appear until postnatal Days 6-7 (P6-P7), corresponding to rod outer segment (ROS) disc formation. Rhodopsin was detected at the same developmental stage. The proportion of 11-cis retinyl esters reached a maximum of 40-50% at P15-P20. Thereafter, the proportion dropped, due to more rapid accumulation of the all-trans isomer. Rhodopsin and IRBP increased in parallel with ROS elongation up to P25, when the ROS had reached their mature lengths. The increases then continued up to P40-P50. In rd (retinal degeneration) mice, IRBP and rhodopsin were identical with the controls until P12, but then dropped as the photoreceptors degenerated. Synthesis and secretion of IRBP in vitro was less than 10% of the controls in rd retinas at P26, when only 4-5% of the photoreceptors survived. The quantities of retinyl esters (mainly stearate and palmitate in the ratio of 6:1, respectively) stored in dark-adapted mouse eyes progressively increased as the animals aged, representing 0.5 mole eq. of the rhodopsin at 8 months. Although retinyl esters (11-cis and all-trans) also accumulated in rd mouse eyes up to P12, little further increase occurred. At P93, the retinyl esters (0.01 nmole X eye-1) were only 4% of the controls at P91. A peak in the proportion of 11-cis isomer occurred at P10-P20, but it averaged only 15% of the total ester and declined to 5% at P93. These findings support the hypothesis that IRBP is synthesized by the rods and cones, and suggest that its synthesis and secretion are initiated when the photoreceptor inner segments start to differentiate. 11-cis Retinoids and rhodopsin do not appear until the outer segments start to form. It is suggested that in the rd mouse the absence of photoreceptors, perhaps coupled with lack of normal interphotoreceptor matrix, leads to a loss in the ability of the pigment epithelium to store retinyl esters.     

Photoreceptor fine structure in the southern fiddler ray (Trygonorhina fasciata).

The fine structure of the retinal photoreceptors has been studied by light and electron microscopy in the southern fiddler ray or guitarfish (Trygonorhina fasciata). The duplex retina of this species contains only rods and single cones in a ratio of about 40:1. No multiple receptors (double cones), no repeating pattern or mosaic of photoreceptors and no retinomotor movements of these photoreceptors were noted. The rods are cylindrical cells with inner and outer segments of the same diameter. Cones are shorter, stouter cells with a conical outer segment and a wider inner segment. Rod outer segment discs display several irregular incisures to give a scalloped outline to the discs while cone outer segment discs have only a single incisure. In all photoreceptors a non-motile cilium joins the inner and outer segments. The inner segment is the synthetic centre of photoreceptors and in this compartment is located an accumulation of mitochondria (the ellipsoid), profiles of both rough and smooth endoplasmic reticulum, prominent Golgi zones and frequent autophagic vacuoles. The nuclei of rods and cones have much the same chromatin pattern but cone nuclei are invariably located against or particularly through the external limiting membrane (ELM). Numerous Landolt's clubs which are ciliated dendrites of bipolar cells as well as Müller cell processes project through the ELM, which is composed of a series of zonulae adherentes between these cells and the photoreceptors. The synaptic region of both rods (spherules) and cones (pedicles) display both invaginated (ribbon) synapses and superficial (conventional) synapses with cones showing more sites than the rods.     

Characterization of SPACR, a sialoprotein associated with cones and rods present in the interphotoreceptor matrix of the human retina: immunological and lectin binding analysis

Rod and cone photoreceptors project from the outer retinal surface into a carbohydrate-rich interphotoreceptor matrix (IPM). Unique IPM glycoconjugates are distributed around rods and cones. Wheat germ agglutinin (WGA) strongly decorates the rod matrix domains and weakly decorates the cone matrix domains. This study characterizes the major WGA-binding glycoprotein in the human IPM, which we refer to as SPACR (sialoprotein associated with cones and rods). SPACR, which has a molecular weight of 147 kDa, was isolated and purified from the IPM by lectin affinity chromatography. A polyclonal antibody to SPACR was prepared that colocalizes in tissue preparations with WGA-binding domains in the IPM. Sequential digestion of SPACR with N- and O- glycosidases results in a systematic increase in electrophorectic mobility, indicating the presence of both N- and O-linked glycoconjugates. Complete deglycosylation results in a reduction in the relative molecular mass of SPACR by about 30%. Analysis of lectin binding allowed us to identify some of the structural characteristics of SPACR glycoconjugates. Treatment with neuraminidase exposes Galbeta1- 3GalNAc disaccharide as indicated by positive peanut agglutinin (PNA) staining, accompanied by the loss of WGA staining. Maackia amurensis agglutinins (MAA-1 and MAA-2), specific for sialic acid in alpha2-3 linkage to Gal, bind SPACR, while Sambucus nigra agglutinin (SNA), specific for alpha2-6 linked sialic acid, does not, indicating that the dominant glycoconjugate determinant on SPACR is the O-linked carbohydrate, NeuAcalpha2-3Galbeta1-3GalNAc. The abundance of sialic acid in SPACR suggests that this glycoprotein may contribute substantially to the polyanionic nature of the IPM. The carbohydrate chains present on SPACR could also provide sites for extensive crosslinking and participate in the formation of the ordered IPM lattice that surrounds the elongate photoreceptors projecting from the outer retinal surface.      

Characteristics of Rod Regeneration in a Novel Zebrafish Retinal Degeneration Model Using N-Methyl-N-Nitrosourea (MNU)

Primary loss of photoreceptors caused by diseases such as retinitis pigmentosa is one of the main causes of blindness worldwide. To study such diseases, rodent models of N-methyl-N-nitrosourea (MNU)-induced retinal degeneration are widely used. As zebrafish (Danio rerio) are a popular model system for visual research that offers persistent retinal neurogenesis throughout the lifetime and retinal regeneration after severe damage, we have established a novel MNU-induced model in this species. Histology with staining for apoptosis (TUNEL), proliferation (PCNA), activated Müller glial cells (GFAP), rods (rhodopsin) and cones (zpr-1) were performed. A characteristic sequence of retinal changes was found. First, apoptosis of rod photoreceptors occurred 3 days after MNU treatment and resulted in a loss of rod cells. Consequently, proliferation started in the inner nuclear layer (INL) with a maximum at day 8, whereas in the outer nuclear layer (ONL) a maximum was observed at day 15. The proliferation in the ONL persisted to the end of the follow-up (3 months), interestingly, without ongoing rod cell death. We demonstrate that rod degeneration is a sufficient trigger for the induction of Müller glial cell activation, even if only a minimal number of rod cells undergo cell death. In conclusion, the use of MNU is a simple and feasible model for rod photoreceptor degeneration in the zebrafish that offers new insights into rod regeneration.     

Detection of interphotoreceptor retinoid binding protein (IRBP) mRNA in human and cone-dominant squirrel retinas by in situ hybridization

Interphotoreceptor retinoid binding protein (IRBP) is a soluble glycolipoprotein located between the neurosensory retina and pigment epithelium, which may serve to transport vitamin A derivatives between these tissues. The specific cell type responsible for IRBP synthesis has not been well established. To address this issue, we have examined the expression of IRBP mRNA in human and cone-dominant ground squirrel retinas by in situ hybridization. Optimal labeling and histological resolution were achieved with 35S- and 3H-labeled anti-sense riboprobes made from a human IRBP cDNA clone, and semi-thin wax-embedded retinal sections. In human retina, label was localized over the inner segments of both rod and cone photoreceptors. Quantitative analysis demonstrated a fourfold higher density of label over rod inner segments. In ground squirrel retina, labeling was found almost exclusively over the inner segments of cones. The results indicate that in human retina both rods and cones express IRBP mRNA, albeit at different levels. In cone-dominant species such as the ground squirrel, cones are the principal cell type responsible for IRBP mRNA synthesis.     

The fine structure of the pigment epithelium and photoreceptor cells of the newt,Triturus viridescens dorsalis (Rafinesque)

The morphology of the retinal pigment epithelium and photoreceptor cells has been studied in the common newt Triturus viridescens dorsalis by light, conventional transmission and scanning electron microscopy. The pigment epithelium is formed by a single layer of low rectangular cells, separated by a multilayered membrane (Bruch's membrane) from the vessels of the choriocapillaris. The scleral border of the pigment epithelium is highly infolded and each epithelial cell contains smooth endoplasmic reticulum, myeloid bodies, mitochondria, lysosomes, phagosomes and an oval nucleus. Inner, pigment laden, epithelial processes surround the photoreceptor outer and inner segments. The three retinal photoreceptor types, rods, single cones and double cones, differ in both external and internal appearance. The newt, rod, outer segments appear denser than the cones in both light and electron micrographs, due to a greater number of rod lamellae per unit distance of outer segment and to the presence of electron dense intralamellar bands. The rod outer segments possess deep incisures in the lamellae while the cone lamellae lack incisures. Both rod and cone outer segments are supported by a peripheral array of dendritic processes containing longitudinal filaments which originate in the inner segment. The inner segment mitochondria, forming the rod ellipsoid, arelong and narrow while those in the cone are spherical to oval in shape. The inner segments of all three receptor cell types also contain a glycogen-filled paraboloid and a myoid region, just outside the nucleus, rich in both rough and smooth endoplasmic reticulum. The elongate, cylindrical nuclei differ in density. The rod nuclei are denser than those of the cones, contain clumped chromatin and usually extend further vitreally. Similarly, the cytoplasm of the rod synaptic terminal is denser than its cone counterpart and contains synaptic vesicles almost twice as large as those of the cones. Photoreceptor synapses in rods and cones are established by both superficial and invaginated contacts with bipolar or horizontal cells.     

Retinal photoreceptor fine structure in the red-backed salamander (Plethodon cinereus).

The retinal photoreceptors of the red-backed salamander (Plethodon cinerus) have been studied by light and electron microscopy. Rods and single cones are present in this duplex retina in a ratio of about 25:1. The photoreceptors in this amphibian species are much larger than is reported for most vertebrates. In the light-adapted state, rods reach deep into the retinal epithelial (RPE) layer. The rod outer segment is composed of discs of uniform diameter displaying several very deep incisors. The rod inner segment displays a distal elliposid of mitochondria and a short stout myoid region. Rod nuclei are electron dense and often protrude through the external limiting membrane. Rod synaptic spherules are large and display several invaginated synaptic sites as well as superficial synapses. It is felt that the rods do not undergo retinomotor movements. The cone photoreceptors are much smaller than the rods and display a tapering outer segment, an unusual modified ellipsoid and a large parabolid of glycogen in the inner segment. Cone nuclei are less electron dense than rods and are located at all levels within the outer nuclear layer. The synaptic pedicle of the cones is larger, more electron lucent and display more synaptic sites (both invaginated and superficial) than that of rods. It is felt that cone photomechanical responses are minimal.     

Modeling the role of mid-wavelength cones in circadian responses to light

Nonvisual responses to light, such as photic entrainment of the circadian clock, involve intrinsically light-sensitive melanopsin-expressing ganglion cells as well as rod and cone photoreceptors. However, previous studies have been unable to demonstrate a specific contribution of cones in the photic control of circadian responses to light. Using a mouse model that specifically lacks mid-wavelength (MW) cones we show that these photoreceptors play a significant role in light entrainment and in phase shifting of the circadian oscillator. The contribution of MW cones is mainly observed for light exposures of short duration and toward the longer wavelength region of the spectrum, consistent with the known properties of this opsin. Modeling the contributions of the various photoreceptors stresses the importance of considering the particular spectral, temporal, and irradiance response domains of the photopigments when assessing their role and contribution in circadian responses to light.